tbuckley/cabot-search huggingface dataset:
Abstract 205: Vadilation Of Neuron-specific Enolase In Cardiac Arrest Patients And Association Factors For Neurological Outcomes In The Subgroup Of Negative Neuron-specific Enolase
Authors: Byungkook Lee, Dong H Lee
Journal: Circulation (2022)

Aim: Neuron-specific enolase (NSE) alone has limitations in prognostication in cardiac arrest survivors, like other tools. To avoid early withdrawal of life-sustaining therapy, we verified the prognostic performance according to the reference value of NSE and investigated the variables related to the neurological outcomes in the patients with negative NSE. Methods: We performed a retrospective analysis of data from adult cardiac arrest survivors who underwent targeted temperature management at a university-affiliated hospital between January 2014 and December 2020. We measured the NSE level 48 hr after the return of spontaneous circulation. We performed receiver operating characteristics (ROC) and used the reference value of NSE (&lt; 17 μg/L), the Youden index indicated NSE, and European Resuscitation Council (ERC) suggested NSE value (&lt; 60 μg/L) as a threshold. We performed a multivariable logistic regression analysis to investigate the independent factors associated with true negative versus false negative for NSE cutoff. The primary outcome was 6-month neurological outcomes with Cerebral Performance Category (CPC), dichotomized into good (CPC 1 or 2) or poor (CPC 3-5) neurologic outcomes. Results: Of the 522 included patients, 355 (68.0%) patients had poor neurological outcomes. The area under ROC of NSE was 0.887 (95% confidence intervals [CIs], 0.856-0.913; p &lt; 0.001) with Youden index value of 35.6 μg/L. Analyses with specific cutoff values of 17 μg/L, 35.6 μg/L, and 60 μg/L showed a sensitivity of 86.8%, 72.4%, and 58.0% with a specificity of 66.5%, 93.4%, and 98.8%, respectively. In the patients with NSE &lt; 60 μg/L, younger age (odd ratio [OR], 0.954 [95% CIs, 0.934-0.976]), witness of collapse (OR, 3.520 [95% CIs, 1.625-7.626]) shockable rhythm (OR, 5.953 [95% CIs, 2.879-12.308]), cardiac etiology (OR, 2.796 [95% CIs, 1.444-5.416]), and lower sequential organ failure assessment (SOFA) (OR, 0.823 [95% CIs, 0.744-0.912]) were independently associated with true negative group rather than false negative group. Conclusions: NSE &lt; 60 μg/L had less than 2% false-positive rate. Younger age, a witness of collapse, shockable rhythm, cardiac etiology, and lower SOFA were associated with good neurological outcomes in the negative NSE group.
Abstract 224: Rate Of Rehabilitation Referral After Cardiac Arrest Based On Socioeconomic Status
Authors: Peter Prescott, Ramsha Khan, Jonathan D Ledyard, Ankur A Doshi, Clifton W Callaway, Jonathan Elmer, Kate Flickinger
Journal: Circulation (2022)

Cardiac arrest (CA) survivors often suffer physical and cognitive deficits. Unlike survivors of myocardial infarction or stroke, CA survivors are inconsistently referred to rehabilitation services. Social and structural determinants of health affects access to care. We investigated if rehabilitation referral rates for CA survivors differed across race, ethnicity, sex and socioeconomic status (SES) based on median income of patient’s zip code of residence. We included consecutive CA survivors discharged from a single academic medical center 2014-2019. We performed a structured chart review to identify referrals to inpatient or outpatient rehabilitation. Outpatient services included cardiac rehabilitation, PT/OT, and speech therapy. We used Census data to determine median household income for each patient’s zip code of residence. We used Fisher’s Exact test and Kruskal Wallis tests to investigate the difference in referral rates based on income brackets identified from Census data, age, sex, race, and ethnicity. We included 674 CA patients, of whom 367 (54%) arrested out of hospital, 418 (62%) were male, median age was 60 (IQR 49-69) years, 526 (78%) were white, 553 (82%) were non-Hispanic or Latin-x. Overall 387 (57%) were referred to rehabilitation ( n=316 (47%) inpatient-only, n=42 (6%) outpatient-only, n=29 (4%) both). Rehabilitation referral differed across categories of income (p=0.023) (Figure) but showed no consistent trend across consecutive categories. Age was positively associated with referral (odds ratio per decade 1.33; 95% CI 1.21-1.47, p=0.015). There was no association of race, ethnicity or sex with rehabilitation referral. In our single center data, referral to rehabilitation increased with age and was less frequent for patients from neighborhoods with the lowest median income. It did not differ based on sex, race or ethnicity. Future studies should investigate rehabilitation attendance rates in comparison to SES.
Abstract 15561: A Rare Case of Air Embolus in the Presence of Bilateral Pulmonary Emboli
Authors: Zohaib V Khan, Hiba Zafar, Kishan V Patel
Journal: Circulation (2022)

Case Presentation: A 70-year-old male with cardiac risk factors, cirrhosis, stage II cholangiocarcinoma, and a right internal jugular port-a-catheter, presented to the hospital following an unwitnessed syncopal episode one day after undergoing a therapeutic paracentesis. On presentation he was hemodynamically unstable and endorsed severe substernal chest pain. Diagnostic work-up revealed large bilateral pulmonary emboli, and large amounts of intravascular gas in the right brachial vein, superior vena cava (SVC), right atrium and ventricle (Figure A). He was immediately placed on supplemental oxygen, given intravenous fluids, and started on vasopressors. He was a poor candidate for mechanical thrombectomy thus tissue plasminogen activator (tPA) was administered, and he was admitted to the medical intensive care unit for further management. Discussion: Venous air emboli occur as rare complications of trauma or intravascular procedures when air or gas enters the vasculature. Symptoms are generally non-specific making them difficult to recognize. In this patient, a central port-a-catheter had been placed two months prior for chemotherapy administration. A central line provides a direct connection between the air and the vasculature. The sub-atmospheric pressures in the SVC, where these lines often terminate, create a pressure gradient conducive to the development of air emboli. Hypovolemic states as seen in cirrhosis and pulmonary emboli) can further magnify this gradient. Interestingly, the presence of a large venous air embolism and concurrent massive bilateral pulmonary emboli, has rarely been previously reported. Caution should be taken in prevention, early detection, and treatment to avoid potentially fatal complications.
Abstract 15511: Sex-Specific Trends in Obesity-Attributable Atrial Fibrillation in the United States
Authors: Sojin Y Wass, Sadeer Al-Kindi
Journal: Circulation (2022)

Introduction: The prevalence of atrial fibrillation (AF) has significantly increased in the United States over the past 2 decades. Obesity is a major risk factor for AF, and the association between obesity and AF may vary by sex. We sought to investigate sex-specific trends in obesity-attributable AF in the US Methods: We used data from the 2019 Global Burden of Disease Study to determine changes in age-standardized AF disability-adjusted life years (DALYs) and mortality in the US between 1990 and 2019. We examined the trends in the contribution of obesity to AF mortality and DALYs by sex. Results: Between 1990 and 2019, age-standardized AF DALYs increased by 13% in males (181 to 205 per 100K) and by 15% in females (110 to 126 per 100K). Age-adjusted AF mortality increased by 22% in males (4.9 to 6.0 per 100K) and by 26% in females (3.5 to 4.4 per 100K). Overall, obesity contributed to higher percentage of AF in females compared with males. Between 1990 and 2019, the percentage of obesity-attributed AF DALYs increased in females (27% to 34%) and males (21% to 31%). The percentage of obesity-attributed AF deaths increased both in females (25% to 32%) and males (18% to 28%) between 1990 and 2019, figure. Conclusion: AF morbidity and mortality showed a disproportionate increase among females compared with males in the US over the past 3 decades. Obesity disproportionately contributes to AF morbidity and mortality among females compared with males.
Abstract 15752: Differential IgG Repertoire in Individuals With Chagas Cardiomyopathy
Authors: Gabriela Venturini, Taniela Bes, Tomasz Kula, Mamie Li, Ellen Shrock, Stephen Elledge, Ester Cerdeira Sabino, Jose Krieger, Alexandre Pereira, Jonathan G Seidman, Christine E Seidman
Journal: Circulation (2022)

Chagas cardiomyopathy (CC) is caused by the infection of Trypanosoma cruzi ( T. cruzi ) and represents a major etiology for heart failure in Latin America. Trying fill gaps related to humoral response in CC, we used a PhIP-Seq technology to describe differential IgG profile between individuals with CC and individuals infected by T. cruzi , but without symptoms (Indeterminate - IND). We built a library comprising all T. cruzi proteome (12766 proteins) and incubated against 1293 serum samples: 396 T. cruzi seronegative samples (98 controls and 298 individuals with cardiomyopathy caused by other causes than Chagas disease) and 897 T. cruzi seropositive samples (684 CC and 213 IND). 1870 peptides were increased in T. cruzi seropositive IgG compared to T. cruzi seronegative samples. Peptides from Nucleoporin NUP149, a flagellar attachment zone protein, basal body protein, surface protein TolT and cytoskeleton associated protein were the peptides with highest IgG response. Using as little as 5 peptides, I derived a classifier model for T. cruzi infection with 97% accuracy. Then, I compared CC and IND samples using logistic regression models after splitting our sample into 2 cohort groups. From these, 316 peptides were significantly different between CC and IND: 289 peptides were increased in CC (27% of them belong to the trans-sialidase class) and 27 peptides were increased in IND (FDR&gt;0.01). Aiming to develop a classifier to separate CCC from IND, I analyzed our data using machine learning approaches. LASSO returned the best model using 48 peptides, with 70% of accuracy, 74% of sensitivity and 69% of specificity. The peptides selected for the model belong to 38 proteins, 21% being unknow function proteins, 18% trans-sialidases, 8% flagellar associated proteins, and 60S ribosomal protein, Nucleoporins and R27-2 proteins classes representing 5% each. Ninety (90%) of selected peptides in LASSO were identified in the previous results using the logistic regression model. I showed for the first time that Chagas Cardiomyopathy individuals have a differential IgG profile against T. cruzi proteins compared to IND individuals. I described a differential IgG response against 84 sequences (62 increased in CCC and 22 increased in IND) that can be related to disease development.
Abstract 15608: Validation of Enhancer/Silencer Activity of the Intracranial Aneurysm-Associated SNP at SOX17 in Primary Human Endothelia
Authors: Vincent M Tutino, Kerry Poppenberg, Adnan H Siddiqui, Jim Jarvis, Lee Chaves
Journal: Circulation (2022)

Introduction: GWAS have identified multiple SNPs that occur more commonly in those with intracranial aneurysms. Many SNPs are located in noncoding genomic regions, suggesting that genetic risk may operate on functional regulatory elements that influence gene expression. However, regulatory elements are most often only indirectly identified through methods such as DNAse hypersensitivity without direct assessment of activity. Hypothesis: We hypothesize CRISPR mediated ablation of putative regulatory elements located within intergenic loci associated with IA will result in mRNA transcript modulation of genes located within the respective topology associated domain. Methods: We investigated a SNP within a haplotype block near SOX17. The haplotype was predicted to have active enhance activity, and to mediate SOX17 expression, based on assessment of its topologically associated domain. Lentiviral constructs (each with unique antibiotic resistance and fluorescent protein reporters) for the expression of Cas9 nuclease and two gRNAs flanking a putative element located at chr8:54412191-54413910 were transfected into the Lenti-X viral propagating cell line (Figure, left). Viral supernatants were transduced into primary HUVEC cells by spinfection with 5 ug/mL polybrene. After antibiotic selection and fluorescence validation, mRNA was isolated, and transcripts quantified through PCR. Results: Lentiviral transduction of HUVECs resulted in CRISPR-mediated removal of the enhancer element located within the haplotype block chr8:54397171-54415556 and resulted in a substantial increase of the SOX17 gene mRNA located within its topology associated domain (Figure, right). Conclusions: CRISPR mediated ablation was used to efficiently remove and validate a genomic element with putative regulatory activity in HUVECs. The methods will be employed to study additional regulatory elements with IA associations as well as other primary vascular cells.
Abstract 15687: Triglyceride Levels and Non-Alcoholic Fatty Liver Disease: A Multivariable Mendelian Randomization Study
Authors: Eloi Gagnon, Emilie Gobeil, Jerome Bourgault, Benoit Arsenault
Journal: Circulation (2022)

Introduction: Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the adult population worldwide. Individuals with NAFLD are twice as likely to develop atherosclerotic cardiovascular diseases compared to individuals without NAFLD. Whether plasma triglyceride levels increase NAFLD risk independently of other lipoprotein subfractions, and hence represent a potential therapeutic target for NAFLD, is unknown. Our objective was to investigate the causal effect of genetically predicted plasma lipids levels on NAFLD using multivariable Mendelian randomization. Methods: We performed univariable and multivariable two-sample MR to investigate the respective causal contribution of triglycerides, apolipoprotein B (apoB), and HDL-C on NAFLD. As genetic instruments for HDL-C, triglycerides and apo B levels, we selected all robustly (p&lt;5e-8) and independently (linkage disequilibrium R2 &lt; 0.001) genetic variants from genome-wide association studies in the UK Biobank (n = 441,016). As outcome, we included the largest NAFLD GWAS (8434 cases and 770,614 controls). Results: In univariable MR analysis, triglyceride levels were robustly associated with NAFLD risk (OR = 1.32, 95% CI=1.20-1.48, p=2.8e-7). In multivariable MR analysis, triglycerides remained robustly associated with NAFLD risk upon adjustment for other correlated lipoprotein subfraction (adjusted OR = 1.30, 95% CI = 1.12-1.51, p = 5.1e-4) (Figure). These results were consistent across a range of sensitivity analyses (MVMR-lasso, MVMR-Egger and MVMR-Median). Conclusions: Results of this two-sample MR study revealed that genetically predicted triglyceride levels may increase the risk of NAFLD independently of other lipoprotein subfraction. These results suggest that triglyceride lowering in the prevention of NAFLD might warrant further investigation.
Abstract 15612: Association Between ECG-Derived Age With Coronary Artery Calcium
Authors: Mohammad Ali Sheffeh, Jose R Medina-Inojosa, Betsy Medina-Inojosa, Zachi Attia, Rosana Bianchettin, Abraham Baez Suarez, Amir Lerman, Paul Friedman, Francisco Lopez-Jimenez
Journal: Circulation (2022)

Introduction: We have previously shown that ECG-derived age (ECG-Age) predicts all-cause and cardiovascular (CV) mortality, reflecting physiologic age. We hypothesized that ECG-Age minus chronological age (Age-Gap) would be associated with coronary artery calcium (CAC) assessed by computer tomography. Methods: We developed a neural network model to predict ECG-Age using 12 lead ECGs from 399,750 training, 99,977 validation and 275,056 testing patients. We then applied the algorithm to 41,202 consecutive patients that from 1997-2020 underwent clinically indicated CAC and ECG within 1 year. Major modifiable CV risk factors were collected as part of preventive cardiology or general medical evaluations. Exclusion criteria were statin therapy, pacemakers, or history of coronary artery disease. Results: We included 41,202 subjects (68.5% males, 83.6% Caucasian), mean chronological age was 55.2±9.1 yrs and the ECG-Age was 56.01±9.3 yrs. The mean Age-Gap was -0.78±7 yrs, R 2 =0.78, p&lt;0.0001. Mean CAC score was 140.2±532.3, and 21,483 (52%) had CAC &gt;0. After adjustment for age and sex, those older by ECG (defined as having a positive Age-Gap) were more likely to have CAC&gt;0 (OR 1.35, 95% CI 1.34-2.37 for those with &gt;1 but &lt;2 SD of a positive Age-Gap; and OR 1.80, 95% CI 1.34-2.37 for those with ≥2 SD of a positive Age-Gap), while those younger by ECG were less likely to have any CAC (OR 0.70, 95% CI 0.57-0.87 for those with &gt;1 but &lt;2 SD of a negative Age-Gap; and OR 0.75, 95% CI 0.67-0.84 for those with ≥2 SD of a negative Age-Gap), respectively. This association remained significant after multivariate adjustment, Fig. A and increased with CAC burden, Fig. B , all P for trend &lt;0.01. Conclusions: The difference between physiologic AI-ECG age and chronologic age, something likely representing rate of biological aging, is associated with presence of CAC, further supporting the hypothesis that AI-ECG age can identify people more likely to have subclinical coronary atherosclerosis.
Abstract 15919: Adverse Outcomes Related Amiodarone Toxicity in Early Rhythm Control of Patients With Atrial Fibrillation: A Nationwide Cohort Study
Authors: Ha Jeong Lim, Pil-sung Yang, Jung-Hoon Sung, BOYOUNG JOUNG
Journal: Circulation (2022)

Background: Early rhythm control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients who had recently (within 1 year) been diagnosed with atrial fibrillation (AF). In real-world data, the most commonly selected initial rhythm control strategy was the Class III anti-arrhythmic drug (AAD) amiodarone, but adverse outcomes related amiodarone toxicity was not well reported in this population. This study sought to investigate the fatal and non-fatal adverse outcomes related amiodarone toxicity in early rhythm control of patients with AF. Methods: Using the database of Korean National Health Insurance Service, we analyzed the adverse outcomes related amiodarone toxicity in 140,908 (rhythm control: 57,148, rate control: 83,760) patients with AF undergoing rhythm control or rate control therapy, initiated within 1 year of AF diagnosis, between 2005 and 2015. Results: The most commonly used rhythm control strategy was the class III drug amiodarone (22,877 (40.0%) of 57,148 patients in early rhythm control), followed by class Ic drugs. Patients with amiodarone for initial rhythm control strategy showed higher rate of interstitial lung disease (1.43% vs. 0.75%, p&lt;0.001), sudden cardia arrest duet to Torsade de Pointes (0.31% vs. 0.17%, p=0.001), and hypothyroidism (16.5% vs. 8.12%, p&lt;0.001). But incidence rate of bradycardia needing a temporary pacemaker, bradycardia needing a permanent pacemaker, and toxic hepatitis were higher in early rhythm control patients with other AADs compared to patients with amiodarone. Conclusions: The most commonly used rhythm control strategy was amiodarone in AF patients undergoing early rhythm control. Using amiodarone for the initial rhythm control strategy showed a higher rate of interstitial lung disease, sudden cardia arrest duet to Torsade de Pointes, and hypothyroidism. Attention should be paid to amiodarone toxicity in selecting rhythm control strategy for these patients.
Abstract 15684: Prognostic Value of Cardiac Damage Staging in Adults With Repaired Coarctation of Aorta
Authors: Kartik Andi, Dhanya Ramachandran, Omar Abozied, Ahmed Goda, Alexander C Egbe
Journal: Circulation (2022)

Background: Chronic left ventricular (LV) pressure overload is common in adults with repaired coarctation of aorta (COA). However, there is no validated systematic approach for assessing cardiac remodeling and damage in this population. The purpose of this study was to evaluate the role of cardiac damage staging scheme (validated for calcific aortic stenosis) for prognostication in adults with repaired COA. Methods: Patients were classified using a modified cardiac damage scheme: stage 0 (no cardiac damage), stage 1 (LV damage), stage 2 (left atrial damage), stage 3 (pulmonary vascular/tricuspid valve damage), and stage 4 (right ventricular damage). Results: Of 795 patients (age 36±16 years), 270 (34%) had stage 0, 198 (25%) had stage 1, 225 (28%) had stage 2, 37 (5%) had stage 3, and 65 (8%) had stage 4 cardiac damage. The 795 patients were followed for 7.3 (2.8-9.6) years, and 94 (12%) died, of which 75 (9%) were cardiovascular deaths. Cardiac damage stage was independently associated with all-cause mortality (adjusted HR 1.31, 95% CI 1.22-1.40, per unit increase in stage), and cardiovascular mortality (adjusted HR 1.42, 95% CI 1.28-1.55, per unit increase in stage). The addition of the cardiac damage stage to the base model (clinical and echocardiographic variables) provided significant incremental improvement in the prediction of 5-year risk of all-cause mortality over the base model (net reclassification index 0.39, p&lt;0.001). Hypertension was associated with cardiac damage and mortality. Conclusions: The cardiac damage scheme can be used for risk stratification, and potentially guide therapy in the COA population.
Abstract 15879: Impact of Pulmonary Hypertension on In-Hospital Outcomes for Patients Undergoing Typical Atrial Flutter Ablation
Authors: Mukunthan Murthi, Ufuk Vardar, Ramtej Atluri, Dae Yong Park, Anoj Shahi
Journal: Circulation (2022)

Introduction: Pulmonary hypertension (PHT) is a progressive disease with a clinical course characterized by frequent decompensations in advanced stages. Atrial arrhythmias, including typical atrial flutter, are common in patients with PHT. We sought to investigate the effect of presence of pulmonary hypertension to the outcomes after typical atrial flutter ablation. Methods: We utilized the National Inpatient database from 2016 to 2019 to perform this study. By utilizing the ICD-10-CM codes all hospitalizations for typical atrial flutter ablation were identified. Patients with atypical flutter and ablation were excluded. Among these subjects, those with associated diagnosis of pulmonary hypertension (WHO Group 1 to 5) were identified and they formed the study group. Primary outcome was to in-hospital mortality and complications. Secondary outcomes included analysis of patient clinical characteristics, length of hospital stay (LOS) and total hospital charges (TOTCH). Multivariate regression analysis was used to predict outcomes. Results: A total of 7,784 patients with PHT were hospitalized for typical atrial flutter ablation during the study period. Patients with PHT were slightly older (66 vs 67 years, p&lt;0.001). The proportion of males was lower in the PHT group (57vs 67 %, p&lt;0.001). For Typical AFL patients undergoing ablation, the presence of PHT was associated with higher odds of mortality (a0R= 1.8, p=0.003), acute kidney injury (a0R= 1.6, p&lt;0.001), heart failure exacerbation (a0R= 1.3, p&lt;0.001) and cardiogenic shock (a0R= 2.2, p&lt;0.001) on multivariate regression analysis. They also had higher LOS (+2.3 days, p&lt;0.001) and TOTCH (+$30,501, p&lt;0.001). Conclusion: Our data shows that pulmonary hypertension is independently associated with worse in-hospital outcomes in patients undergoing typical atrial flutter ablation, including higher mortality. Further prospective studies are required to confirm our findings.